Intracranial pressure ("ICP") is usually approximated by the cerebral spinal fluid ("CSF") pressure. CSF pressure is usually measured by means of a spinal tap which involves puncturing the subarachnoid space of the spinal cord. For numerous diseases this must be done repeatedly to monitor treatment results or disease progression. Such invasive monitoring is associated with risk and discomfort and is not always feasible.
The invention allows measurement of the ICP to be made in a simpler and far less painful way than prior methods. This type of measurement would be non-invasive and would not involve a spinal tap. In fact, the patient may simply look into a retinal scanner in order to allow the measurement to be taken. This invention can be used to measure ICP in patients or environments where other techniques of ICP measurement are not feasible or practical, such as during space flight.
The invention takes advantage of the fact that ICP may be sensed from appropriate measurements of portions of the eye. In particular, and referring to FIG. 1 (A), the sclera 16 is a firm fibrous membrane that serves to maintain the form of the eye globe and does not change with changes in intraocular pressure. The choroid 18 is a thin, vascular layer which covers the posterior five-sixths of the globe. Choroid 18 is pierced behind by an optic nerve 12 which is covered by a nerve sheath 14. The optic nerve sheath is fibrous, inelastic and continuous with the sclera of the eye and the dural covering of the brain. Choroid 18 is fixed to sclera 16. The inner surface of choroid 18 is covered by retina 22. A thin cribriform lamina (the lamina cribrosa ) is formed at the point where optic nerve 12 passes through sclera 16. The minute orifices in this region serve for the passage of nerve fibers.(see FIG. 1 (B).
The intracranial pressure and pressure within the optic nerve sheath have been shown to be approximately equal. In cadaveric studies, the optic nerve pressure changes almost immediately with changes in ICP. The relationship of optic nerve pressure to ICP has been shown to be substantially linear (essentially 1:1) with optic nerve pressure being generally slightly less than ICP.
The intraocular pressure ("IOP") is higher than the ICP under normal circumstances (e.g., IOP:12-20 mm Hg supine; ICP:7-14 mm Hg supine; ICP:0-2 mm Hg standing). IOP and ICP transmit hydrostatic forces to opposite sides of the lamina cribrosa (also referred to as the scleral canal). Both blood flow and axoplasmic flow through the lamina cribrosa may be restricted in proportion to the amount of differential pressure. Exposure to such differential pressures can bow the lamina cribrosa anteriorly if ICP&gt;IOP, or posteriorly if ICP&lt;IOP, producing the clinical conditions of papilledema and glaucoma, respectively. Measurement of changes in the anterior-posterior position of the optic nerve head relative to a fixed structure such as the sclera or choroid, while simultaneously measuring intraocular pressure, allows for calculation of intracranial pressure.
Prolonged ICP&gt;IOP results in papilledema. Papilledema describes the ophthalmoscopic appearance of the optic nerve head when the axons of the optic nerve head and retinal nerve fiber layer ("NFL") become swollen from restricted axoplasmic flow. There may be a twenty-fold thickening of the nerve fibers under such circumstances. Papilledema only occurs when there is patency between the subarachnoid spaces of the optic nerve and the brain, so that ICP can be transmitted to the optic nerve.
Ophthalmoscopically visible papilledema can be seen within 2 -4 hours of onset of highly elevated ICP. Sensitive techniques for measurement of NFL thickness in the retina or optic nerve head may detect early papilledema before it becomes visible with the ophthalmoscope. Measurement of NFL thickness with simultaneous measurment of IOP would also permit calculation of ICP.
Optical coherence tomography ("OCT")is a technique which may be used to monitor the early morphologic changes of the optic nerve head associated with changes in ICP or IOP quantifiably. It avoids the vagaries introduced by processing and interpretation of prior techniques such as color fundus photography. In addition, OCT can detect axonal swelling earlier than other imaging techniques (e.g., stereoscopic fundus photography, optic nerve head analyzers, ophthalmoscopy) because these techniques depend upon changes in surface topography.
OCT can measure NFL thickness or relative anterior-posterior position of the optic nerve head regardless of changes in surface topography.
Refinement of OCT to study ICP may in addition lead to the ability to measure other systemic or intraocular parameters non-invasively. For instance, measurements of retinal blood flow with OCT Doppler techniques can be used to study indices such as pH or pCO2 when other parameters which control retinal blood flow are known.